Journal Article
A synthetic peptide as an allosteric inhibitor of human arginase I and II
Kai Gao; Sergey Lunev; Mariska P. M. van den Berg; Zayana M. Al-Dahmani; Stephen Evans; Dyon A. L. J. Mertens; Herman Meurs; Reinoud Gosens; Matthew R. Groves
Molecular Biology Reports · Vol. 48, Issue 2 · pp. 1959-1966 · 2021
Abstract
Arginine metabolism mediated by arginases plays a critical role in cell and tissue function. The arginine hydrolysis is deeply involved in the urea cycle, which helps the kidney excrete ammonia from blood. Upregulation of arginases affects microenvironment stability due to the presence of excess urea in blood. To regulate the arginase activities properly, a synthetic peptide based on the structure of human arginase I was designed and assessed. Preliminary data shows it inhibits human arginase I and II with an IC 50 of 2.4 ± 0.3 and 1.8 ± 0.1 mmol, respectively. Our kinetic analysis indicates the inhibition is not competitive with substrate – suggesting an allosteric mechanism. This result provides a step towards specific inhibitors design.